Is BTNL9 p.Pro357Arg (c.1070C>G) pathogenic?

BTNL9 p.Pro357Arg (c.1070C>G) is classified Uncertain significance in BTNL9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). AlphaMissense: likely benign (0.0761); Absent from gnomAD v4.1.

How common is BTNL9 p.Pro357Arg (c.1070C>G) in the general population?

BTNL9 p.Pro357Arg (c.1070C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BTNL9 p.Pro357Arg (c.1070C>G)?

AlphaMissense predicts likely benign (score 0.0761) — an in-silico prediction, not a clinical call.

BTNL9 p.Pro357Arg

c.1070C>G · VCV4216901

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0761 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0761	likely benign
REVEL	0.001	strongly benign-leaning
SaProt	LLR -6.85	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.7
Regional constraint	o/e 1.07	unconstrained · MANE · 14 kb · p 0.044 · regional, not allelic
Overall
CADD	0.022	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BTNL9
Protein: p.Pro357Arg
Coding: c.1070C>G
MANE Select: NM_152547
Type: single nucleotide variant
Location: chr5:181059324 (GRCh38)
Gene constraint: LOEUF 1.325 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.28
Residue 357: the b30.2/spry domain; the 'disordered' region

Full BTNL9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BTNL9 p.Ala144Pro Uncertain significance ★ ⚠ same type
BTNL9 p.Ala200Val Uncertain significance ★ ⚠ same type
BTNL9 p.Ala252Val Uncertain significance ★ ⚠ same type
BTNL9 p.Ala261Thr Uncertain significance ★ ⚠ same type
BTNL9 p.Ala273Thr Uncertain significance ★ ⚠ same type
BTNL9 p.Ala291Glu Uncertain significance ★ ⚠ same type
BTNL9 p.Ala314Thr Uncertain significance ★ ⚠ same type
BTNL9 p.Ala335Thr Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/btnl9-p-pro357arg (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown